Known techniques for asymmetrically synthesizing optically active alcohols useful as intermediates of pharmaceuticals, liquid crystal materials, and the like include a process comprising asymmetric hydrogenation using baker's yeast and a process comprising asymmetric hydrogenation using a specific catalyst.
In particular, with respect to asymmetric hydrogenation of .beta.-ketonic acid derivatives to obtain optically active alcohols, it has been reported that the asymmetric hydrogenation can be carried out by using a rhodium-optically active phosphine complex as a catalyst. For example, J. Solodar reports in Chemtech., 421-423 (1975) that asymmetric hydrogenation of methyl acetoacetate gives methyl 3-hydroxybutyrate in an optical yield of 71% ee.
Further, asymmetric hydrogenation using a tartaric acid-modified nickel catalyst has been proposed. According to this technique, asymmetric hydrogenation of methyl acetoacetate gives methyl 3-hydroxybutyrate in an optical yield of 85% ee as disclosed in Tai, Yukagaku, 822-831 (1980).
On the other hand, considerable literature exists on the preparation of carnitine. For example, known processes for preparing carnitine include a process comprising reacting epichlorohydrin with prussic acid and trimethylamine to obtain cartinonitrile and hydrolyzing the resulting cartinonitrile as disclosed in E. Strack et al., Chem. Ber., Vol. 86, 525 (1953); a process comprising reacting a 4-chloro-3-hydroxybutyric acid alkyl ester with a trialkylamine as disclosed in JP-B-37-5172 (the term "JP-B" as used herein means an "examined published Japanese patent application"); a process comprising reacting a diketene compound with chlorine, reacting the product with an optically active amino acid methyl ester to obtain an optically active amino acid amide as a diastereomer as disclosed in JP-A-61-271261 (the term "JP-A" as used herein means an "unexamined published Japanese patent application"); and a process comprising reducing an ethyl .gamma.-chloroacetoacetate with baker's yeast to obtain optically active ethyl 3-hydroxybutyrate and reacting the product with trimethylamine as disclosed in J. Am. Chem. Soc., Vol. 105, 5925-5926 (1983).
In preparing optically active alcohols, although the process using baker's yeast produces an alcohol having relatively high optical purity, the resulting optically active alcohol is limited in absolute configuration, and synthesis of an enantiomer is difficult.
The process utilizing asymmetric hydrogenation of .beta.-ketonic acid derivatives in the presence of a rhodium-optically active phosphine complex does not produce an alcohol having sufficient optical purity. Besides, metallic rhodium to be used in the catalyst is expensive due to limitations in place and quantity of production. When used as a catalyst component, it forms a large proportion of the cost of the catalyst, ultimately resulting an increase in cost of the final commercial products.
The process using a tartaric acid-modified nickel catalyst involves disadvantages of difficulty in preparing the catalyst and insufficient optical yield.
In general, recovery of an active substance by optical resolution is not economical because it requires an optically active substance in an amount equimolar to a substrate and the undesired enantiomer is useless or should be subjected to racemization for re-resolution.
The asymmetric hydrogenation using baker's yeast essentially involves separation of the produced optically active substance from the yeast.